Parachlorometaxylenol is listed in the Merck Index as 4-chloro-3,5-dimethyl phenol, and is often called PCMX, as it will be referred to hereinafter. The structural formula of PCMX is: ##STR1##
PCMX is a well known antimicrobial compound that has about 60 times the germicidal potency of carbolic acid.
It is practically insoluble in water. Only about one gram of PCMX will dissolve in about 3 liters of water at 20.degree. C. A concentrated solution of PCMX in pure water at ambient temperature contains only about 0.03% of the compound on a weight to weight basis.
At low concentrations up to about 3.75% by weight in any vehicle, PCMX is considered to be relatively non-toxic and non-irritating to human skin. In principle, water should be the best solvent vehicle for applying PCMX in solution to human skin since it is the least toxic and least irritating to humans, and produces the fewest deleterious side effects.
Therefore, aqueous solutions of PCMX should be the best liquid for adding PCMX to such products as cosmetics, toiletries, personal care products, surgical scrubs, and items which are applied to human skin.
However, because of its low solubility in water, it has been difficult or impossible heretofore to prepare aqueous compositions containing PCMX in germicidally effective concentrations of about 0.5% or above.
Adding a water soluble solvent such as ethanol or acetone to water or aqueous compositions does permit higher concentrations of PCMX in the solvent vehicle. But a low concentration of organic solvent in water or aqueous compositions does not increase appreciably the solubility of PCMX. Furthermore, since organic solvents irritate human skin, aqueous compositions containing higher concentrations of an organic solvent are of questionable value in such consumer products as cosmetics, toiletries, and personal care items which must remain on the skin for considerable periods of time after application.
High concentrations of organic solvents present additional problems in manufacturing because of their volatility and flammability.
In the past, higher concentrations of PCMX have been prepared by making oil-in-water emulsions or dispersions. In such preparations, PCMX is dissolved almost entirely in the oil phase. But in such two phase systems, the anti-microbial activity of PCMX depends on its concentration in the aqueous phase. Therefore the germicidal properties of an emulsion having a PCMX component is relatively very low with respect to its PCMX content.
Aqueous compositions containing higher concentrations of PCMX have been prepared in the past with the aid of water soluble non-ionic surfactants having polyoxyethyl chains. In these surfactant-water systems, the solubility of PCMX appears to be proportional to the concentration of non-ionic surfactants (J. PHARM. AND PHARMACOL. 8 774-80, 1956). However, it has been shown that non-ionic surfactants reduce considerably the germicidal effectiveness of lipophilic PCMX in aqueous vehicles (CA 73 2884l2g, and CA 73 28843 h). Therefore, in order to obtain the desired antimicrobial effectiveness of aqueous compositions containing both PCMX and a non-ionic surfactant, higher concentrations of PCMX would be required. This, in turn, would require higher concentrations of non-ionic surfactant until the concentration of PCMX delivers the required antimicrobial activity.
However, it is well known that non-ionic surfactants can produce irritation in humans, especially if left on the skin for extended periods of time. Therefore, the combination of a non-ionic surfactant and a higher concentration of PCMX would increase the amount of skin irritation when used together as components of cosmetics, toiletries, personal care products, and surgical scrubs.
In view of the fact that PCMX is not soluble enough in water to prepare aqueous solutions of high enough concentration to be practical as antimicrobials, it would be a significant advance in the art to find a way of increasing the solubility of PCMX in aqueous media without attenuating its antimicrobial properties, and without adding components which irritate human skin. It would also be useful to be able to prepare compositions or concentrated solutions of PCMX that are completely soluble in aqueous media so that they can be diluted easily to yield clear aqueous solutions of PCMX of desired concentration with a high degree of germicidal activity and a low degree of skin irritability.